Adenosine A1 receptor agonist, N6-cyclohexyladenosine, protects myelin and induces remyelination in an experimental model of rat optic chiasm demyelination; electrophysiological and histopathological studies

Asghari, Ali; Azarnia, Mahnaz; Mirnajafi‐Zadeh, Javad; Javan, Mohammad

doi:10.1016/j.jns.2012.11.008

Cited by 27 publications

(15 citation statements)

References 35 publications

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“…12,18,19 VEP has been used in animal models to assess neurological or potential eff ects on remyelination of the adenosine A1 receptor agonist N6-cyclohexyladenosine and siRNAs against the Nogo receptor. 20,21 VEP was also used in single or small multicentre clinical studies assessing high-dose intravenous immunoglobulin, erythropoietin, simvastatin, and phenytoin in patients with acute optic neuritis, [22][23][24][25] and in natural recovery observational studies after an acute optic neuritis episode. 12,16,17,[26][27][28] When baseline characteristics of participants enrolled in RENEW were compared with those in trials of other candidate remyelinating or neuroprotective drugs, age and percentage of women were similar, mean number of days from fi rst acute optic neuritis symptom to fi rst dose was 24 days in RENEW versus 5-20 days in previous acute optic neuritis studies.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial

Cadavid

Balcer

Galetta

et al. 2017

The Lancet Neurology

232

220

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial

Cadavid

Balcer

Galetta

et al. 2017

The Lancet Neurology

232

220

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“…This model of demyelination is reversible, and lysolecithin is quickly decomposed and removed, and repair of myelin occurs over several days. [ 16 ] Thus, by eliminating the primary cause of damage, probably immune responses began to decline and reached to the normal at the day 7.…”

Section: Discussionmentioning

confidence: 99%

“…The lesion groups received an injection of 2 μl of 1% lysolecithin (Sigma, St. Louis, USA) prepared in sterile 0.9% saline, pH 7.4, into the chiasm. [ 16 ] The sham groups underwent the same surgical procedures, but the same volume of saline was injected instead of lysolecithin.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon-gamma in Rat Model of Multiple Sclerosis

et al. 2017

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Background:There is an increase in inflammatory and a reduction in anti-inflammatory cytokines in multiple sclerosis (MS). Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin-10 (IL-10) and interferon gamma (IFN-γ) in animal models of MS.Materials and Methods:To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 μg/kg) for 21 days. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay at 7, 14, and 21 days after that.Results:The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL-10 compared to the sham group (P < 0.05) at 7th day, but this increase was prevented by all doses of levothyroxine. IFN-γ was decreased significantly (P < 0.001) 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN-γ significantly.Conclusion:The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses.

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“…The lesion groups received an injection of 2 μl of 1% lysolecithin (Sigma, St. Louis, USA) prepared in sterile 0.9% saline, pH 7.4, into the chiasm. [ 13 ] The sham group underwent the same surgical procedures, but the same volume of saline was injected instead of lysolecithin. The solutions were injected within 3 min, and the needle was kept in place for another 5 min to avoid the possible reflux through the needle path.…”

Section: Methodsmentioning

confidence: 99%

Effects of levothyroxine on visual evoked potential impairment following local injections of lysolecithin into the rat optic chiasm

et al. 2018

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Background:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system which has no any known definitive treatment. Studies have shown that thyroid hormones (THs) in addition to their roles in the development of the nervous system and the production of myelin have important roles in the adult's brain function. Since the only way to treat MS is the restoration of myelin, the aim of this study was to evaluate the effects of levothyroxine on visual evoked potential (VEP) impairment following local injections of lysolecithin into the rat optic chiasm.Methods:To induce demyelination, lysolecithin was injected into the optic chiasm of male Wistar rats. VEP recording was used to evaluate demyelination and remyelination before and 10, 17, and 24 days after the lysolecithin injection. The rats received an intraperitoneal injection of levothyroxine with doses 20, 50, and 100 μg/kg in different experimental groups.Results:VEP latency and amplitude showed demyelination at 10 and 17 days after an induced lesion in MS group which was reversed at day 24. Levothyroxine prevented these impairments, especially in high doses.Conclusions:According to the results, lysolecithin-induced demyelination at optic chiasm and VEP impairments can be restored by administration of levothyroxine. Therefore, THs probably have positive effects in demyelinating diseases.

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Adenosine A1 receptor agonist, N6-cyclohexyladenosine, protects myelin and induces remyelination in an experimental model of rat optic chiasm demyelination; electrophysiological and histopathological studies

Cited by 27 publications

References 35 publications

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial

The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon-gamma in Rat Model of Multiple Sclerosis

Effects of levothyroxine on visual evoked potential impairment following local injections of lysolecithin into the rat optic chiasm

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